Abstract
Ferroptosis-related genes play an important role in the progression of lung adenocarcinoma (LUAD). However, the potential function of ferroptosis-related lncRNAs in LUAD has not been fully elucidated. Thus, to explore the potential role of ferroptosis-related lncRNAs in LUAD, the transcriptome RNA-seq data and corresponding clinical data of LUAD were downloaded from the TCGA dataset. Pearson correlation was used to mine ferroptosis-related lncRNAs. Differential expression and univariate Cox analysis were performed to screen prognosis related lncRNAs. A ferroptosis-related lncRNA prognostic signature (FLPS), which included six ferroptosis-related lncRNAs, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high risk-score group and low risk-score group by the median risk score. Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of FLPS. Enrichment analysis showed that the biological processes, pathways and markers associated with malignant tumors were more common in high-risk subgroups. There were significant differences in immune microenvironment and immune cells between high- and low-risk groups. Then, a nomogram was constructed. We further investigated the relationship between six ferroptosis-related lncRNAs and tumor microenvironment and tumor stemness. A competing endogenous RNA (ceRNA) network was established based on the six ferroptosis-related lncRNAs. Finally, we detected the expression levels of ferroptosis-related lncRNAs in clinical samples through quantitative real-time polymerase chain reaction assay (qRT-PCR). In conclusion, we identified the prognostic ferroptosis-related lncRNAs in LUAD and constructed a prognostic signature which provided a new strategy for the evaluation and prediction of prognosis in LUAD.
Highlights
MATERIALS AND METHODSLung cancer is the disease with the highest morbidity and mortality, among which lung adenocarcinoma (LUAD) is accounted for 40–50% of all lung cancer cases (Bray et al, 2018)
Our study showed 33 Long non-coding RNAs (lncRNAs) were differentially expressed in LUAD and correlated with prognosis
A lncRNA whose expression value was correlated with one or more of the 18 ferroptosisrelated genes was defined as a ferroptosis-related lncRNA
Summary
Lung cancer is the disease with the highest morbidity and mortality, among which lung adenocarcinoma (LUAD) is accounted for 40–50% of all lung cancer cases (Bray et al, 2018). We retrieved ferroptosis-related genes from previous studies and mined potential dysregulated ferroptosisrelated lncRNAs through bioinformatic analysis, based on the LUAD dataset of TCGA. The RNA-seq transcriptome data, including 497 LUAD samples and 54 adjacent normal tissues, and corresponding clinical data were extracted from TCGA database for differential expression analysis. Expressed genes (DEGs), miRNAs (DEMs) and lncRNAs between tumor and adjacent normal tissues were identified by using the “limma” or “edgeR” R package (| log2FC| > 1, FDR < 0.05). Univariate Cox analysis of overall survival (OS) was performed to screen ferroptosis-related genes and lncRNAs with prognostic value. Expressed genes (DEGs), miRNAs (DEMs), and lncRNAs between tumor and adjacent normal tissues were identified by Wilcox test. Comparison of gene expression between the normal and tumors were performed in 18 cancer types which had more than five associated adjacent normal samples using linear mixed effects models. Mann–Whitney U test was used to compare the ssGSEA scores of immune cells or pathways between the high-risk and low-risk group
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